Mass spectrometry (MS) is a central analytical technology that finds a large variety of applications in a broad range of fields, especially when coupled with a chromatographic separation technique such as gas chromatography (GC) or liquid chromatography (LC). Since a growing fraction of compounds that need to be analyzed are either thermally labile or with a low volatility (low volatiles), the use of LC-MS is growing recently at a faster rate than GC-MS. However, GC-MS still possesses a major advantage over LC-MS of having an automated sample identification through the use of extensive 70 eV electron ionization (EI) libraries.
In the past, a method named particle beam was developed that enabled the combination of LC and MS with electron ionization and its associated advantage of automated library search and sample identification. The particle beam method was, however, confounded with problems of limited sensitivity, non-linear response, ion source induced peak tailing and limited range of samples amenable for analysis in view of excessive sample degradation at the ion source. In addition, standard electron ionization mass spectra suffer from a well-known “long felt need” of enhancing the relative abundance of the molecular ion which is missing or very weak in the EI mass spectra of about half of the particle beam LCL-MS sample compounds. Without having a trustworthy molecular ion, sample identification with the library cannot be trusted, in view of possible interference from homologous and degradation compounds and the identification of samples that are not included in the library, is practically precluded. Consequently, the particle beam method was phased out from the market and currently LC-MS analyses utilize almost exclusively electrospray ionization (ESI) and/or atmospheric pressure chemical ionization (APCI) for sample ionization.
Recently a method and apparatus for LC-MS has been developed which is based on spray formation and full solvent and sample vaporization before or inside a supersonic nozzle, supersonic expansion of the vaporization sample and solvent and its vibrational cooling in a supersonic molecular beam (SMB) followed by its electron ionization as cold molecules in the SMB. (A. Amirav, U.S. Pat. No. 7,247,495 and O. Granot and A. Amirav, Int. J. Mass. Spectrom. 244, 15-28 (2005)). This method has proven to be more sensitive than the particle beam, provides linear response and is compatible with an increased range of compounds in view of the elimination of sample degradation at the ion source. Most importantly, enhanced molecular ion and mass spectral information is provided due to the ionization of vibrationally cold sample molecules in the SMB. Automated library based sample identification was enabled and demonstrated with very good matching factors to the library MS in view of the feature of enhanced molecular ion combined with all the EI standard fragments. Furthermore, relatively uniform response was demonstrated to both polar and non-polar sample compounds.
This method of electron ionization LC-MS with SMB, however, suffers from a major problem (in addition to a few other problems) of poor robustness in view of too frequent clogging of the solvent delivery tube. This problem of poor robustness is further exacerbated by the need to open the vacuum chamber each time that the clogged solvent delivery tube has to be serviced or replaced, followed by lengthy cycles of pump down and MS and ion source and optics tuning.
The first and essential step in the vaporization of any flowing liquid (solution) as arriving from the LC is the formation of spray, and preferably mono-dispersed spray with small spray droplets. The standard methods of spray formation that has been used so far for sample vaporization are pneumatic assisted nebulization or thermally assisted spray and/or their combination. However, since with SMB all the added gas that is used for pneumatic assisted nebulization and spray formation is discharged into the vacuum, this mode of spray formation is considered as highly undesirable with SMB. The reason for this perception is that due to limited upper flow rate acceptance (also named “throughput”) of the turbo molecular pump of the nozzle chamber, every added one ml/min gas flow rate reduces the maximum allowed LC liquid flow rate by about one micro liter/min. Thus, since the nebulization gas must be fully exhausted into the vacuum chamber, pneumatic spray that is frequently used in many other applications such as ICP-AE and ICP-MS was not used for LC-MS with SMB and thermally assisted spray was chosen instead.
The use of thermally assisted spray that is also known as Thermospray, however, requires the heating of the sample solution at the solvent delivery tube, and this heating results in frequent solvent delivery tube clogging. As the solution is heated, a portion of the sample precipitates or decomposes, particularly with concentrated solutions or when thermally labile sample compounds are analyzed which degrade, and gradually a layer of hard residue is build like limestone in a domestic kettle up to a full clogging. In addition, the output edge of the solvent delivery tube is unavoidably located inside the spray and sample vaporization tube, and this edge also suffers from a tendency to periodically clog. For this reason Thermospray was occasionally referred to in the literature as a method of “spray and pray” and this major clogging problem is reported in several publications in peer reviewed journals.
Thus, there is a major need for improved method and device for having effective electron ionization LC-MS.